A novel lncRNA ROPM-mediated lipid metabolism governs breast cancer stem cell properties DOI Creative Commons
Shuiqing Liu, Yan Sun, Yixuan Hou

et al.

Journal of Hematology & Oncology, Journal Year: 2021, Volume and Issue: 14(1)

Published: Oct. 29, 2021

Cancer stem cells (CSCs) are considered as the major cause to tumor initiation, recurrence, metastasis, and drug resistance, driving poor clinical outcomes in patients. Long noncoding RNAs (lncRNAs) have emerged crucial regulators cancer development progression. However, limited lncRNAs involved CSCs been reported.The novel lncROPM (a regulator of phospholipid metabolism) breast (BCSCs) was identified by microarray validated qRT-PCR BCSCs from tissues. The significance evaluated two cohorts TANRIC database (TCGA-BRCA, RNAseq data). Gain- loss-of-function assays were performed examine role on both vitro vivo. regulatory mechanism investigated bioinformatics, RNA FISH, pull-down, luciferase reporter assay, actinomycin D treatment. PLA2G16-mediated metabolism determined UHPLC-QTOFMS system. Cells' chemosensitivity assessed CCK8 assay.LncROPM is highly expressed BCSCs. enhanced exists clinic tumors other solid positively correlates with malignant grade/stage prognosis studies show that required for maintenance properties Mechanistically, regulates PLA2G16 expression directly binding 3'-UTR increase mRNA stability. increased significantly promotes production free fatty acid, especially arachidonic acid BCSCs, thereby activating PI3K/AKT, Wnt/β-catenin, Hippo/YAP signaling, thus eventually involving stemness. Importantly, notably contribute chemo-resistance. Administration using therapeutic drugs such doxorubicin, cisplatin, or tamoxifen combined Giripladib (an inhibitor cytoplasmic phospholipase A2) can efficiently eliminate tumorigenesis.Our study highlights its target play roles sustaining BCSC may serve a biomarker cells. Targeting lncROPM-PLA2G16 signaling axis be strategy patients cancer.

Language: Английский

Role of RNA modifications in cancer DOI
Isaia Barbieri, Tony Kouzarides

Nature reviews. Cancer, Journal Year: 2020, Volume and Issue: 20(6), P. 303 - 322

Published: April 16, 2020

Language: Английский

Citations

938
Cancer Immune Evasion Through Loss of MHC Class I Antigen Presentation DOI Creative Commons
Karthik Dhatchinamoorthy, Jeff D. Colbert, Kenneth L. Rock

et al.

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: March 9, 2021

Major histocompatibility class I (MHC I) molecules bind peptides derived from a cell's expressed genes and then transport display this antigenic information on the cell surface. This allows CD8 T cells to identify pathological that are synthesizing abnormal proteins, such as cancers expressing mutated proteins. In order for many arise progress, they need evolve mechanisms avoid elimination by cells. MHC not essential survival therefore one mechanism which can evade immune control is losing antigen presentation machinery (APM). Not only will impair ability of natural responses cancers, but also frustrate immunotherapies work re-invigorating anti-tumor cells, checkpoint blockade. Here we review evidence loss frequent occurrence in cancers. We discuss new insights into some common underlying through inactivate pathway consider possible strategies overcome limitation ways could restore tumors improve immunotherapy.

Language: Английский

Citations

703
Long noncoding RNAs in cancer metastasis DOI
Siyuan Liu, Ha X. Dang, Daniel A. Lim

et al.

Nature reviews. Cancer, Journal Year: 2021, Volume and Issue: 21(7), P. 446 - 460

Published: May 5, 2021

Language: Английский

Citations

504
RETRACTED ARTICLE: m6A mRNA methylation initiated by METTL3 directly promotes YAP translation and increases YAP activity by regulating the MALAT1-miR-1914-3p-YAP axis to induce NSCLC drug resistance and metastasis DOI Creative Commons

Dan Jin,

Jiwei Guo, Yan Wu

et al.

Journal of Hematology & Oncology, Journal Year: 2019, Volume and Issue: 12(1)

Published: Dec. 9, 2019

Abstract Background METTL3 is an RNA methyltransferase that mediates m 6 A modification and implicated in mRNA biogenesis, decay, translation. However, the biomechanism through which regulates MALAT1-miR-1914-3p-YAP axis activity to induce NSCLC drug resistance metastasis not very clear. Methods The expression of was analyzed by qPCR assays. Protein levels were western blotting immunofluorescent staining. Cellular proliferation detected CCK8 Cell migration invasion wound healing transwell assays, respectively. Promoter activities gene transcription luciferase reporter Finally, MeRIP. Results increased YAP . METTL3, YTHDF3, YTHDF1, eIF3b directly promoted translation interaction with initiation machinery. Moreover, level MALAT1 due a higher mediated METTL3. Meanwhile, stability METTL3/YTHDF3 complex. Additionally, functions as competing endogenous sponges miR-1914-3p promote via YAP. Furthermore, reduction knockdown inhibits tumor growth enhances sensitivity DDP vivo. Conclusion indicated methylation initiated promotes recruiting YTHDF1/3 complex increases regulating axis. metastasis.

Language: Английский

Citations

403
Antisense Oligonucleotides: An Emerging Area in Drug Discovery and Development DOI Open Access
Karishma Dhuri,

Clara Bechtold,

Elias Quijano

et al.

Journal of Clinical Medicine, Journal Year: 2020, Volume and Issue: 9(6), P. 2004 - 2004

Published: June 26, 2020

Antisense oligonucleotides (ASOs) bind sequence specifically to the target RNA and modulate protein expression through several different mechanisms. The ASO field is an emerging area of drug development that targets disease source at level offers a promising alternative therapies targeting downstream processes. To translate ASO-based into clinical success, it crucial overcome challenges associated with off-target side effects insufficient biological activity. In this regard, chemical modifications diverse delivery strategies have been explored. review, we systematically discuss modifications, mechanism action, optimized classes ASOs. Further, highlight recent advances made in drugs focus on are approved by Food Drug Administration (FDA) European Medicines Agency (EMA) for applications. We also various candidates trials, outstanding opportunity microRNA as viable therapeutic future therapies.

Language: Английский

Citations

394
The Role of Inflammation in Diabetic Retinopathy DOI Creative Commons
John V. Forrester, Lucia Kuffová, Mirela Delibegović

et al.

Frontiers in Immunology, Journal Year: 2020, Volume and Issue: 11

Published: Nov. 6, 2020

Inflammation is central to pathogenic processes in diabetes mellitus and the metabolic syndrome particularly implicates innate immunity development of complications. a primary event Type 1 where infectious (viral) / or autoimmune initiate disease; contrast, chronic inflammation typical 2 considered sequel increasing insulin resistance disturbed glucose metabolism. Diabetic retinopathy (DR) perceived as vascular neurodegenerative disease which occurs after some years poorly controlled diabetes. However, many clinical features DR are late events reflect nature retinal architecture its cellular composition. Retinal microvascular is, fact, an early pathogenetically, induced by low grade, persistent leukocyte activation causes repeated episodes capillary occlusion and, progressive, attritional ischemia. The later, overt signs consequence Metabolic dysregulation involving both lipid metabolism may lead activation. On molecular level, we have shown that macrophage-restricted protein tyrosine phosphatase 1B (PTP1B) key regulator it possible PTP1B underlie disease. We also adherent CCR5+CD11b+ monocyte macrophages appear be selectively involved occlusion. In this review, discuss relationship between later DR, common pathogenetic diabetic other retinopathies, mechanisms whereby hyperglycemia dyslipidemia, signaling disease, interventions prevent these retinopathies. address role for adaptive DR. Although significant improvements treatment been made with intravitreal anti-VEGF therapy, sizeable proportion patients, sight-threatening macular edema, fail respond. Alternative therapies targeting inflammatory offer advantage.

Language: Английский

Citations

290
Long noncoding RNAs: functions and mechanisms in colon cancer DOI Creative Commons
Sian Chen, Xian Shen

Molecular Cancer, Journal Year: 2020, Volume and Issue: 19(1)

Published: Nov. 28, 2020

Abstract Evidence indicates that long non-coding RNAs (lncRNAs) play a crucial role in the carcinogenesis and progression of wide variety human malignancies including colon cancer. In this review, we describe functions mechanisms lncRNAs involved oncogenesis, such as HOTAIR, PVT1, H19, MALAT1, SNHG1, SNHG7, SNHG15, TUG1, XIST, ROR ZEB1-AS1. We summarize roles regulating cell proliferation, apoptotic death, cycle, migrative invasive ability, epithelial-mesenchymal transition (EMT), cancer stem cells drug resistance addition, briefly highlight circRNAs tumorigenesis progression, circPPP1R12A, circPIP5K1A, circCTIC1, circ_0001313, circRNA_104916 circRNA-ACAP2. This review provides rationale for anticancer therapy via modulation circular (circRNAs) carcinoma.

Language: Английский

Citations

267
Identification of tumor immune infiltration-associated lncRNAs for improving prognosis and immunotherapy response of patients with non-small cell lung cancer DOI Creative Commons
Jie Sun, Zicheng Zhang, Siqi Bao

et al.

Journal for ImmunoTherapy of Cancer, Journal Year: 2020, Volume and Issue: 8(1), P. e000110 - e000110

Published: Feb. 1, 2020

Background Increasing evidence has demonstrated the functional relevance of long non-coding RNAs (lncRNAs) to immunity regulation and tumor microenvironment in non-small cell lung cancer (NSCLC). However, immune infiltration-associated lncRNAs their value improving clinical outcomes immunotherapy remain largely unexplored. Methods We developed a computational approach identify an lncRNA signature (TILSig) as indicator infiltration patients with NSCLC through integrative analysis for lncRNA, profiles 115 lines, 187 lines 1533 NSCLC. Then influence TILSig on prognosis was comprehensively investigated. Results Computational profiling identified consisting seven associated infiltration. The significantly stratified into immune-cold group immune-hot both training validation cohorts. These exhibit improved survival outcome greater compared patients. Multivariate revealed that is independent predictive factor after adjusting other factors. Further accounting checkpoint gene discriminatory power similar expression levels genes prolonged observed low implying better response inhibitor (ICI) immunotherapy. Conclusions Our finding importance evaluating infiltrate highlighted potential coupled specific factors biomarkers ICI enable more precise selection

Language: Английский

Citations

253
Distinct Processing of lncRNAs Contributes to Non-conserved Functions in Stem Cells DOI Creative Commons
Chunjie Guo,

Xu-Kai Ma,

Yu‐Hang Xing

et al.

Cell, Journal Year: 2020, Volume and Issue: 181(3), P. 621 - 636.e22

Published: April 1, 2020

Language: Английский

Citations

250
Epigenetics in hepatocellular carcinoma DOI
Ganji Purnachandra Nagaraju, Begum Dariya, Prameswari Kasa

et al.

Seminars in Cancer Biology, Journal Year: 2021, Volume and Issue: 86, P. 622 - 632

Published: July 26, 2021

Language: Английский

Citations

206